CoChat
Sign Up
Cited by 69Enzyme Structure and FunctionProtein Structure and DynamicsCrystal structures of chemical compounds

CMM—An enhanced platform for interactive validation of metal binding sites

Open access
Gucwa, Michal, Lenkiewicz, Joanna, Zheng, Heping, Cymborowski, Marcin, Cooper, David R., Murzyn, Krzysztof, Minor, Wladek·2023·Protein Science
DOI 10.1002/pro.4525PMC PMC9794025
Open this paper in CoChat — free accountOpen PDF

Abstract

Metal ions bound to macromolecules play an integral role in many cellular processes. They can directly participate in catalytic mechanisms or be essential for the structural integrity of proteins and nucleic acids. However, their unique nature in macromolecules can make them difficult to model and refine, and a substantial portion of metal ions in the PDB are misidentified or poorly refined. CheckMyMetal (CMM) is a validation tool that has gained widespread acceptance as an essential tool for researchers working on metal‐macromolecule complexes. CMM can be used during structure determination or to validate metal binding sites in structural models within the PDB. The functionalities of CMM have recently been greatly enhanced and provide researchers with additional information that can guide modeling decisions. The new version of CMM shows metals in the context of electron density maps and allows for on‐the‐fly refinement of metal binding sites. The improvements should increase the reproducibility of biomedical research. The web server is available at https://cmm.minorlab.org.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1002/pro.4525

Cites

3 of 3 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Accurate metal assignments are not trivial, and even structures determined by X-ray crystallography have had metals assigned incorrectly.

    “However, accurate metal assignments are not trivial, and even structures determined by X-ray crystallography (where anomalous scattering can provide relevant information) have had metals assigned incorrectly.68”

    From Metals in Motion: Understanding Labile Metal Pools in Bacteria (2025) · cites this paper as [68]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 31

  1. Brown A, Long F, Nicholls RA, Toots J, Emsley P, Murshudov G. Tools for macromolecular model building and refinement into electron cryo‐microscopy reconstructions. Acta Crystallogr D Biol Crystallogr. 2015; 71: 136– 53. 25615868 PMC4304694
  2. Burley SK, Berman HM, Bhikadiya C, Bi C, Chen L, Di Costanzo L, et al. RCSB Protein Data Bank: biological macromolecular structures enabling research and education in fundamental biology, biomedicine, biotechnology and energy. Nucleic Acids Res. 2019; 47: D464– 74. 10.1093/nar/gky1004/5144139 30357411 PMC6324064 · DOI
  3. Chruszcz M, Domagalski M, Osinski T, Wlodawer A, Minor W. Unmet challenges of structural genomics. Curr Opin Struct Biol. 2010; 20: 587– 97. 20810277 PMC3017768
  4. Cooper DR, Porebski PJ, Chruszcz M, Minor W. X‐ray crystallography: assessment and validation of protein‐small molecule complexes for drug discovery. Expert Opin Drug Discov. 2011; 6: 771– 82. 21779303 PMC3138648
  5. Domagalski MJ, Zheng H, Zimmerman MD, Dauter Z, Wlodawer A, Minor W. The quality and validation of structures from structural genomics. Methods Mol Biol. 2014; 1091: 297– 314. 10.1007/978-1-62703-691-7_21 24203341 PMC4081469 · DOI
  6. Errington TM, Denis A, Perfito N, Iorns E, Nosek BA. Challenges for assessing replicability in preclinical cancer biology. Elife. 2021; 10: 1– 32. PMC8651289 34874008
  7. Handing KB, Shabalin IG, Kassaar O, Khazaipoul S, Blindauer CA, Stewart AJ, et al. Circulatory zinc transport is controlled by distinct interdomain sites on mammalian albumins. Chem Sci. 2016; 7: 6635– 48. 28567254 PMC5450522
  8. Handing KB, Niedzialkowska E, Shabalin IG, Kuhn ML, Zheng H, Minor W. Characterizing metal‐binding sites in proteins with X‐ray crystallography. Nat Protoc. 2018; 13: 1062– 90. 10.1038/nprot.2018.018 29674755 PMC6235626 · DOI
  9. Harding MM, Nowicki MW, Walkinshaw MD. Metals in protein structures: a review of their principal features. Crystallogr Rev. 2010; 16: 247– 302.
  10. Jaskolski M, Wlodawer A, Dauter Z, Minor W, Rupp B. Group depositions to the Protein Data Bank need adequate presentation and different archiving protocol. Protein Sci. 2022; 31: 784– 6. 35000237 PMC8927872
  11. Kleywegt GJ, Jones TA. xdlMAPMAN and xdlDATAMAN ‐ programs for reformatting, analysis and manipulation of biomacromolecular electron‐density maps and reflection data sets. Acta Crystallogr D Biol Crystallogr. 1996; 52: 826– 8. 15299647
  12. Kovalevskiy O, Nicholls RA, Murshudov GN. Automated refinement of macromolecular structures at low resolution using prior information. Acta Crystallogr Sect D Struct Biol. 2016; 72: 1149– 61. 27710936 PMC5053141
  13. Kuppuraj G, Dudev M, Lim C. Factors governing metal‐ligand distances and coordination geometries of metal complexes. J Phys Chem B. 2009; 113: 2952– 60. 19708219
  14. Majorek K, Kuhn ML, Chruszcz M, Anderson WF, Minor W. Double trouble‐buffer selection and his‐tag presence may be responsible for nonreproducibility of biomedical experiments. Protein Sci. 2014; 23: 1359– 68. 25044180 PMC4286991
  15. Murshudov GN, Skubák P, Lebedev AA, Pannu NS, Steiner RA, Nicholls RA, et al. REFMAC5 for the refinement of macromolecular crystal structures. Acta Crystallogr D Biol Crystallogr. 2011; 67: 355– 67. 21460454 PMC3069751
  16. Nicholls RA. Ligand fitting with CCP 4. Acta Crystallogr D Struct Biol. 2017; 73: 158– 70. 28177312 PMC5297919
  17. Niedzialkowska E, Gasiorowska O, Handing KB, Majorek KA, Porebski PJ, Shabalin IG, et al. Protein purification and crystallization artifacts: the tale usually not told. Protein Sci. 2016; 25: 720– 33. 10.1002/pro.2861 26660914 PMC4815408 · DOI
  18. Pozharski E, Weichenberger CX, Rupp B. Techniques, tools and best practices for ligand electron‐density analysis and results from their application to deposited crystal structures. Acta Crystallogr Sect D Biol Crystallogr. 2013; 69: 150– 67. 23385452
  19. Rose AS, Hildebrand PW. NGL viewer: a web application for molecular visualization. Nucleic Acids Res. 2015; 43: W576– 9. 25925569 PMC4489237
  20. Rose AS, Bradley AR, Valasatava Y, Duarte JM, Prlic A, Rose PW. NGL viewer: web‐based molecular graphics for large complexes. Bioinformatics. 2018; 34: 3755– 8. 29850778 PMC6198858
  21. Shabalin IG, Porebski PJ, Minor W. Refining the macromolecular model – achieving the best agreement with the data from X‐ray diffraction experiment. Crystallogr Rev. 2018; 24: 236– 62. 10.1080/0889311X.2018.1521805 30416256 PMC6219471 · DOI
  22. Smart OS, Horský V, Gore S, Svobodová VR, Bendová V, Kleywegt GJ, et al. Validation of ligands in macromolecular structures determined by X‐ray crystallography. Acta Crystallogr Sect F Struct Biol. 2018; 74:228–36. PMC5947763 29533230
  23. Vaguine AA, Richelle J, Wodak SJ. SFCHECK: a unified set of procedures for evaluating the quality of macromolecular structure‐factor data and their agreement with the atomic model. Acta Crystallogr Sect D Biol Crystallogr. 1999; 55: 191– 205. 10089410
  24. Weichenberger CX, Pozharski E, Rupp B. Visualizing ligand molecules in twilight electron density. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2013; 69: 195– 200. PMC3564628 23385767
  25. Winn MD, Ballard CC, Cowtan KD, Dodson EJ, Emsley P, Evans PR, et al. Overview of the CCP4 suite and current developments. Acta Crystallogr D Biol Crystallogr. 2011; 67: 235– 42. 21460441 PMC3069738
  26. Wlodawer A, Minor W, Dauter Z, Jaskolski M. Protein crystallography for non‐crystallographers, or how to get the best (but not more) from published macromolecular structures. FEBS J. 2008; 275: 1– 21. PMC4465431 18034855
  27. Wlodawer A, Minor W, Dauter Z, Jaskolski M. Protein crystallography for aspiring crystallographers or how to avoid pitfalls and traps in macromolecular structure determination. FEBS J. 2013; 280: 5705– 36. 24034303 PMC4080831
  28. wwPDB consortium. Protein Data Bank: the single global archive for 3D macromolecular structure data. Nucleic Acids Res. 2019; 47: D520– 8. 30357364 PMC6324056
  29. Zheng H, Chruszcz M, Lasota P, Lebioda L, Minor W. Data mining of metal ion environments present in protein structures. J Inorg Biochem. 2008; 102: 1765– 76. 18614239 PMC2872550
  30. Zheng H, Hou J, Zimmerman MD, Wlodawer A, Minor W. The future of crystallography in drug discovery. Expert Opin Drug Discov. 2014; 9: 125– 37. 24372145 PMC4106240
  31. Zheng H, Chordia MD, Cooper DR, Chruszcz M, Müller P, Sheldrick GM, et al. Validation of metal‐binding sites in macromolecular structures with the CheckMyMetal web server. Nat Protoc. 2014; 9: 156– 70. 24356774 PMC4410975

Cited by

Sorted by citations

Authors
Gucwa, M., Lenkiewicz, J., Zheng, H., Cymborowski, M., Cooper, D. R., Murzyn, K., & Minor, W.
Affiliations
  • Department of Molecular Physiology and Biological Physics University of Virginia Charlottesville Virginia USA
  • University of Virginia (US)
  • Jagiellonian University (PL)
Corresponding author
  • Murzyn, Krzysztof
  • Minor, Wladek
ORCID
Venue
Protein Science
Publisher
Wiley
Published
2022-12-22
Volume
32
Issue
1
Pages
e4525-e4525
ISSN
  • 0961-8368 (ISSN-L)
  • 1469-896X
DOI
10.1002/pro.4525
PMC
PMC9794025
OpenAlex
W4310671712
Cited by
69
References
3
Citations by year
2026: 12 · 2025: 18 · 2024: 29 · 2023: 10
FWCI
4.51
Type
journal article
Language
en
Open access
Licence
Locations
  • Protein Science (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Jagiellonian University Repository (Jagiellonian University) (submittedVersion, cc-by-nc-nd)
Funders
National Institutes of Health (GM117325, GM132595)
Topics
  • Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Physical Sciences › Chemistry › Inorganic Chemistry › Crystal structures of chemical compounds
Keywords
metal binding sites, metal ion identification, structural validation, electron density maps, protein structure modeling, Protein Data Bank
MeSH terms
Binding Sites, Ions, Metals, Models, Molecular, Proteins, Reproducibility of Results

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review